L. M. Alonso Martinez, J. DaSilva
Oct 20, 2020
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Journal
Journal of labelled compounds & radiopharmaceuticals
Abstract
Candesartan is a clinically-approved angiotensin II type 1 receptor (AT1 R)-blocker that selectively binds AT1 Rs in high affinity. We report here the radiosynthesis and automation of the novel [18 F]fluorobenzyl derivative of Candesartan using the Sonogashira cross-coupling reaction. [18 F]Fluorobenzyl-Candesartan was developed from 4-[18 F]fluoroiodobenzene ([18 F]FIB) that was conjugated with alkyne-trityl-candesartan with the assistance of a Pd (PPh3 )4 /CuI catalyst followed by acid deprotection. The 3-step two-reactor 2-HPLC purification process was automated resulting in >90% pure [18 F]fluorobenzyl-Candesartan ([18 F]7) in a RCY of 4.6±1.1% (decay corrected from EOB) and molar activities of 1406-5513 GBq/mmol. [18 F]FIB was reproducibly obtained by direct radiofluorination of the mono-iodinated triphenylsulfonium salt in the presence of K222/K2 CO3 in a ~30% yield (decay-corrected). [18 F]7 was stable (>97%) up to 4 h in solution and up to 1 h in rat plasma at 37 o C. However, the use of Sonogashira cross-coupling reaction to produce [18 F]fluorobenzyl-Candesartan in high yields and molar activities was found to be challenging for routine use in radiochemistry labs.